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Biomedical subjects

S Erlinger

Publications and source records attributed to S Erlinger.

At least 163 records · Page 9Linked to original sources
PubMed1990

Influence of backward perfusion on ursodeoxycholate-induced choleresis in isolated in situ rat liver.

Ursodeoxycholate-induced bicarbonate-rich hypercholeresis was studied in isolated in situ forward- or backward-perfused rat livers. Both spontaneous bile flow and bile acid secretion were similar regardless of the direction of the perfusion. The choleretic effect of tauroursodeoxycholate infusion (400 nmol.min-1.100 g-1 body weight) was not significantly different in forward- or backward-perfused livers either. Ursodeoxycholate infusions at low rate (800 nmol.min-1.100 g-1 body weight) induced similar bile flow, bile acid output and bicarbonate output in both forward- and backward-perfused livers. Net ursodeoxycholate uptake, measured as [14C]ursodeoxycholate uptake over the bile acid infusion period (30 min), was not significantly different during forward- or backward-perfusion (4.8 and 5.1 mumol/g liver, respectively); i.e., approx. 67% of infused dose (approximately 7.5 mumol/g liver per 30 min). A 2-fold increase in the dose of ursodeoxycholate infusion (1600 nmol.min-1.100 g-1 b.wt.) induced additional enhancement in both bile flow and bicarbonate biliary secretion, but not in bile acid uptake or output, in forward-perfused livers. Moreover, infusion of the same dose of ursodeoxycholate to backward-perfused livers had a significantly lower choleretic effect (-29%, p less than 0.001) even though ursodeoxycholate uptake and biliary output were similar regardless of perfusion direction. Net ursodeoxycholate uptake, was only 2.4 mumol/g liver; i.e., approx. 16% of infused dose (approximately 15 mumol/g liver per 30 min). These findings indicate that a process related with the hepatic microanatomy may be involved in the hypercholeretic response to ursodeoxycholate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Role of intracellular organelles in the hepatic transport of bile acids.

The intracellular events associated with the vectorial transport of bile acids by the hepatocytes from the sinusoidal pole to the canalicular pole are reviewed. Binding to cytosolic proteins occurs. The role of this binding is to prevent efflux from the cytosol back into the blood. There is evidence from electron microscopy, from autoradiography and from immunoperoxidase observations that bile acids interact with the endoplasmic reticulum and the Golgi apparatus. There is also evidence that a carrier system or taurocholate exists on the Golgi membrane. We propose that a vesicular pathway involving the Golgi apparatus and dependent on the integrity of microtubules may play a role in bile acid transport in the cell. Inhibition of bile acid transport by microtubule poisons is consistent with this hypothesis. Finally, monohydroxylated, cholestatic bile acids such as lithocholate and taurolithocholate interact with the endoplasmic reticulum. This interaction results in a depletion of the endoplasmic reticulum calcium stores and an increase in intracellular ionized calcium. The relationship of this novel effect of bile acids to their cholestatic properties remains to be elucidated.

Actin Cytoskeleton↗
PubMed1990

Membranous obstruction of the inferior vena cava and hepatocellular carcinoma in a Caribbean patient.

Membranous obstruction of the inferior vena cava has been reported mainly in South Africa, Japan, and India; in 20-40% of patients the disease is complicated by hepatocellular carcinoma. We report a case of membranous obstruction of the inferior vena cava with hepatocellular carcinoma in a 43-year-old Caribbean man of Indian origin. The Caribbean islands may constitute another geographical area where the population is at risk for the development of membranous obstruction of the inferior vena cava and subsequent hepatocellular carcinoma.

Adult↗
PubMed1990

Retroperitoneal fibrosis after surgery for aortic aneurysm in a patient with periarteritis nodosa: successful treatment with corticosteroids.

A 54-year-old man with hepatitis B virus-related periarteritis nodosa developed retroperitoneal fibrosis with bilateral hydronephrosis 2.5 months after placement of an aortobifemoral prosthesis for abdominal aortic aneurysm. Retroperitoneal fibrosis disappeared after treatment with corticosteroids. This observation is interesting in the light of the hypothesis that retroperitoneal fibrosis is caused by vasculitis.

Aorta, Abdominal↗
PubMed1990

Effect of acid-base balance on biliary bicarbonate secretion in the isolated perfused guinea pig liver.

Secretin-induced choleresis is of ductal origin and involves bicarbonate transport. Its mechanism is unknown. To determine the relative effects of systemic pH, PCO2, and bicarbonate concentration on secretin-stimulated bicarbonate transport, states of acute metabolic and respiratory acidosis or alkalosis were created in isolated perfused guinea pig livers with or without secretin infusion. During spontaneous secretion conditions, biliary bicarbonate secretion was not correlated with perfusate pH (7.19-7.62) or perfusate PCO2 (23.9-59.7) but was significantly correlated with perfusate bicarbonate concentration (17.5-37.9 mM). Under secretion infusion (25 mU/min), bile flow and biliary bicarbonate concentration increased significantly (109 and 51%, respectively). Biliary bicarbonate secretion was not correlated with perfusate pH (7.19-7.60) but was significantly correlated both with perfusate bicarbonate concentration (14.6-36.8 mM) and PCO2 (25.8-54.3 mmHg). Spontaneous and secretin-induced bile flow were correlated with biliary bicarbonate concentration. The correlation between biliary bicarbonate secretion and PCO2 during secretin-induced choleresis supports the hypothesis that secretin-induced biliary bicarbonate secretion could, at least in part, involve a transport of H+ (or OH-) rather than HCO3- itself and that intracellular pH could play a role in the regulation of this secretion. Amiloride (5 X 10(-4) M) did not influence secretin-induced biliary bicarbonate secretion. This result suggests that the Na(+)-H+ exchange is not involved in bicarbonate secretion by ductular cells.

Acid-Base Equilibrium↗
PubMed1990

Recent concepts in bile formation and cholestasis.

Progress has recently been made in the understanding of normal bile secretion mechanisms. The membrane carriers for bile acids have been identified and new insights into intracellular transport mechanisms have been obtained. In particular, characterization of a vesicular pathway involving the Golgi apparatus is well under way. Hypercholeretic bile acids, such as ursodeoxycholic acid, have been discovered. Their choleretic effect is far greater than that of physiological bile acids and they stimulate bicarbonate secretion. Testable hypotheses to explain their hypercholeretic effect have been proposed, in particular the chole-hepatic shunt hypothesis. Several mechanisms capable of inducing cholestasis have been identified: a) inhibition of Na+, K(+)-ATPase; b) increased permeability of the paracellular pathway leading to leakage of bile constituents back into plasma; c) microtubule or microfilament dysfunction; d) increased cytosolic free calcium concentration due to permeabilization of the endoplasmic reticulum calcium stores. It is not yet possible, in a given case, to establish which of these mechanisms is predominant. Several may operate. A better knowledge of the mechanisms involved may lead to improved treatment.

Actin Cytoskeleton↗
PubMed1990

[An increase of choleresis in secondary biliary cirrhosis in rats is caused by bile duct secretion].

Bile flow may be considerably increased in human cirrhosis. The mechanism of this increase has not been established. Two mechanisms have been proposed: a) increased canalicular filtration because of sinusoidal hypertension, or b) secretion by proliferated bile ductules. To distinguish between these two possibilities, we examined the determinants of bile secretion in rats with secondary biliary cirrhosis after bile duct obstruction. Sham-operated animals served as controls. Four weeks after bile duct ligation, all animals had cirrhosis. Bile flow was significantly higher and bile salt secretion significantly lower in cirrhotic animals than in controls. Biliary bicarbonate concentration was significantly higher in cirrhotic animals than in controls. Bile-to-plasma concentration ratio of erythritol was significantly lower in cirrhotic animals than in controls, suggesting a dilution of erythritol by a secretion distal to bile canaliculi. Bile-to-plasma ratio of sucrose was not significantly different in cirrhotics and controls, suggesting that paracellular permeability was not modified. Secretin, at the dose of 3 clinical units/100 g, induced an increase of approximately 75 percent in bile flow, and 70 percent in biliary bicarbonate concentration in cirrhotics. In conclusion, bile flow was increased in biliary cirrhosis in rats. The dilution of erythritol, the increase in biliary bicarbonate concentration and the increased response to secretin strongly suggest that increased choleresis was due, at least in part, to secretion by bile ductules or ducts. These results confirm that secondary biliary cirrhosis is a good experimental model for the study of alterations of bile secretion in cirrhosis.

Animals↗
PubMed1989

Characteristics of bile acid-mediated Ca2+ release from permeabilized liver cells and liver microsomes.

Saponin-treated liver cells and a microsomal fraction were used to characterize the mechanism of the Ca2+ release induced by different bile acids. The saponin-treated cells accumulated 0.8-1 nmol/mg of protein of the medium Ca2+ in a nonmitochondrial, high affinity, and inositol (1,4,5)-trisphosphate (Ins(1,4,5)P3)-sensitive Ca2+ pool. Three of five bile acids tested, lithocholate and the conjugates taurolithocholate and taurolithocholate sulfate, released 85% of the Ca2+ pool within 45-60 s and with ED50 from 16 to 28 microM. Ins(1,4,5)P3 released 80% from the same Ca2+ pool with an ED50 of 0.3 microM. The Ca2+-Mg2+-ATPase inhibitor vanadate (1 mM) had no effect on the Ca2+ released by the bile acids and Ins(1,4,5)P3. The Ins(1,4,5)P3-binding antibiotic neomycin (1 mM) and the receptor competitor heparin (16 micrograms/ml) abolished the releasing effect of Ins(1,4,5)P3 but had no effect on the bile acid-mediated Ca2+ release. The 45Ca2+ accumulated by the microsomal fraction (8 nmol of 45Ca2+/mg of protein) was released by the bile acids within 45-90 s and with an ED50 of 17 microM. In contrast, the bile acids had no effect on the Ca2+ permeability of other natural and artificial membranes. The resting 45Ca2+ influx of intact cells (0.45 nmol/mg of protein/min), the 45Ca2+ accumulated by mitochondria (2-13 nmol of 45Ca2+/mg of protein), and the 45Ca2+ trapped in sonicated phosphatidylcholine vesicles (5 mM 45Ca2+) were not altered by the different bile acids. These results suggest that the Ca2+ release initiated by lithocholate and its conjugates results from a direct action on the Ca2+ permeability of the Ins(1,4,5)P3-sensitive pool. It is not mediated by Ins(1,4,5)P3 or via activation of the Ins(1,4,5)P3 receptor, and it is specific for the membrane of the internal pool.

Animals↗
PubMed1989

Permeability of the rat biliary tree to ursodeoxycholic acid.

The permeability of the biliary epithelium to [14C]ursodeoxycholic acid (UDCA), a hypercholeretic bile acid, was compared to that of the 14C-labeled nonhypercholeretic bile acids cholic acid (CA), taurocholic acid (TCA), and tauroursodeoxycholic acid (TUDCA) by means of anterograde intrabiliary infusions and retrograde intrabiliary injections in the anesthetized rat. Anterograde intrabiliary infusions were performed by perfusing an isolated segment of common bile duct in vivo. After anterograde intrabiliary infusions, the fraction of unrecovered UDCA (that had presumably been absorbed from the biliary lumen) was 11.03 +/- 1.03 (SE)% (n = 6) of the administered dose. It was significantly higher than that of TUDCA (1.25 +/- 0.27%; n = 5; P less than 0.01), CA (2.62 +/- 0.43%; n = 4; P less than 0.01), and TCA (2.57 +/- 0.79%; n = 6; P less than 0.01). In separate experiments, bile was collected from the common bile duct and from the left hepatic duct. UDCA recovered from the left hepatic duct was found in the conjugated form, indicating that, after absorption in the common bile duct, it had been conjugated by the hepatocyte and secreted into bile. After retrograde intrabiliary injections of UDCA and CA, the cumulative percentages of recovered radioactivity were not significantly different (84.50 +/- 2.65 and 87.33 +/- 1.80%, respectively); however, peak recovery of UDCA was significantly delayed compared with that of CA. Moreover, UDCA was recovered mostly in the conjugated form, while CA was recovered mostly in the unconjugated form. These results suggest that, in the rat, UDCA is significantly more absorbed by the biliary tree than CA, TUDCA, and TCA. They support the hypothesis that UDCA undergoes a cholehepatic circulation.

Absorption↗
PubMed1989

[Effect of chronic administration of cyclosporin A on choleresis in rats].

The effect of therapeutic doses of cyclosporine A (CyA) on bile flow and bile salt output was studied in the rat. Thirty male Sprague-Dawley rats (250 to 380 g) were injected intraperitoneally with CyA (n = 15) or vehicle (n = 15) at the dose of 10 mg.kg-1 for 3 weeks. The effect of CyA on basal and taurocholate-induced bile flow, on basal bile salt output and bile salt output under taurocholate infusion, and the effect of chronic administration of CyA on bile salt-independent bile flow was evaluated. Administration of CyA was associated with a decrease in basal bile flow (5.6 +/- 0.7 vs 6.7 +/- 0.7 microliters.min-1.100 g-1; p less than 0.001) and bile flow under taurocholate infusion (8.0 +/- 0.8 vs 10.9 +/- 1.1 microliters.min-1.100 g-1; p less than 0.001). Basal bile salt output (133.9 +/- 48.2 vs 173.8 +/- 53.6 nmol.min-1.100 g-1; p less than 0.003) and bile salt output under the infusion of taurocholate were significantly lower in cyclosporine-treated rats than in controls (443.3 +/- 48.2 vs 617.2 +/- 172.7 nmol.min-1.100 g-1; p less than 0.001). There was no significant difference in bile salt-independent bile flow between the 2 groups. There was no modification of seric alanine aminotransferase activity or hepatic histology. This study confirms that chronic administration of CyA at therapeutic doses can induce cholestasis. Cholestasis is related mainly to a decrease in bile salt secretion and bile salt-dependent flow.

Animals↗
PubMed1989

[Oral dissolving treatment of gallbladder calculi: focus in 1989].

Oral dissolution treatment with chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) is indicated in the case of cholesterol gallstones. However, three conditions must be satisfied for treatment to be effective: 1) the stones must be radiolucent; 2) the gallbladder must be functioning, i.e. opacified by oral cholecystography; 3) the stones must be smaller than 15 mm in diameter. Most authors consider that treatment is only justified when the stones are symptomatic. On the basis of these criteria, it has been estimated that about 20% of patients with gallstones presenting to gastroenterologists could be suitable for treatment. The mean percentage of efficacy is of the order of 50 to 60% at 18 months to 2 years. This percentage may be as high as 70-80% in the case of floating stones smaller than 1 cm. At the optimal dose (15 mg/kg/day), CDCA may induce diarrhoea and raised transaminases. Its prolonged administration can induce hepatic lesions. UDCA (7-10 mg/kg/day) generally does not have any side effect. The combination of CDCA/UDCA at the dose of 7-8 mg/kg/day of each agent may be more effective. After stopping treatment, a recurrence is observed in about 50% of cases within 5 years. Regular ultrasonographic follow-up (annually, for example) is therefore necessary to treat recurrences in time. Because of the criteria of efficacy and its adverse effects, oral dissolution treatment is only indicated in a very limited number of patients. However, it constitutes an essential complement to extracorporeal lithotripsy, which may represent its principal indication at the present time.

Administration, Oral↗
PubMed1988

Release of calcium from the endoplasmic reticulum by bile acids in rat liver cells.

The effects of four bile acids on cell Ca2+ were examined in suspensions of isolated rat hepatocytes. Taurolithocholate and lithocholate which inhibit bile secretion increased the cytosolic Ca2+ concentration (ED50, 25 microM), as measured by the fluorescent indicator quin2, and promoted a net loss of Ca2+ from the cells. This effect resulted from rapid mobilization of Ca2+ from an intracellular Ca2+ store. This store corresponds to the one that is permeabilized by the inositol (1,4,5)trisphosphate-dependent hormone vasopressin. However, taurolithocholate and lithocholate, unlike the hormone, did not induce a significant accumulation of inositol trisphosphate fraction in isolated hepatocytes. In addition, these agents did not alter the cell and the mitochondria membrane permeability to ions. When applied to saponin-permeabilized cells, taurolithocholate and lithocholate released Ca2+ (ED50, 20 microM) from an ATP-dependent, nonmitochondrial pool which is sensitive to inositol (1,4,5)trisphosphate. In contrast, the bile acids taurocholate and cholate, which increase bile secretion, had no effect on cell Ca2+ in intact hepatocytes or in saponin-permeabilized hepatocytes. It is suggested that taurolithocholate and lithocholate permeabilize the endoplasmic reticulum to Ca2+ and that the resulting permeabilization of this compartment may be involved in the inhibition of bile secretion in mammalian liver.

Animals↗
PubMed1988

Effect of the bile acid taurolithocholate on cell calcium in saponin-treated rat hepatocytes.

Neomycin was used to assess the involvement of Ins (1,4,5)P3 in the Ca2+ release from the endoplasmic reticulum induced by the bile acid taurolithocholate. In saponin-permeabilized rat hepatocytes, neomycin via its ability to bind Ins (1,4,5)P3 abolished the release of Ca2+ induced by added Ins (1,4,5)P3. In contrast, it did not alter the Ca2+ release initiated by the bile acid. In intact cells, neomycin had no effect on the [Ca2+]i rises promoted by taurolithocholate and vasopressin. It is suggested that the effect of taurolithocholate in liver is not mediated by Ins (1,4,5)P3 but results from a primary action on endoplasmic reticulum.

Animals↗
PubMed1988

Sensitivity and specificity of microscopic examination of gallbladder bile for gallstone recognition and identification.

During cholecystectomy, gallbladder bile and gallstones were obtained from 77 patients and gallbladder bile was obtained from 39 patients free of stones (11 patients had biliary stenosis). According to their chemical composition, gallstones were classified as cholesterol (n = 46) or pigment (n = 31) stones. In patients with gallstones (a) cholesterol crystals better helped to identify cholesterol gallstones (sensitivity, 87%; specificity, 97%; positive predictive value, 97%) than did an abnormal cholesterol saturation index of bile (sensitivity, 93%; specificity, 48%; positive predictive value, 73%); (b) the presence of cholesterol crystals was significantly related to the cholesterol content of gallstones and the bile cholesterol saturation index; and (c) bilirubinate crystals, when present alone (without cholesterol crystals), were good predictors of pigment gallstones (sensitivity, 71%; specificity, 93%; positive predictive value, 88%). In the absence of stones, bilirubinate crystals were present in 9 of 28 patients without biliary stenosis (4 with alcoholic cirrhosis and 2 with alcoholic pancreatitis) and 8 of 11 patients with biliary stenosis. In the absence of stones, cholesterol crystals were present in 2 of 28 patients without biliary stenosis and in 4 of 11 patients with biliary stenosis, suggesting that bile stasis can induce cholesterol crystal formation.

Adult↗